Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis
Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis
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DOI：
10.1006/brbi.1995.1030
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发表时间：
1995-12-01
影响因子：
15.1
通讯作者：
Ransohoff, RM
中科院分区：
文献类型：
--
作者：
Glabinski, AR;Tani, M;Ransohoff, RM
中枢神经系统（CNS）表达的两种趋化因子mrna，编码单核细胞趋化蛋白-1 （MCP-1）和ifn - γ诱导蛋白（IP-10），先前被证明与小鼠实验性自身免疫性脑脊髓炎（EAE）的临床症状密切相关。趋化因子mrna在星形胶质细胞内积聚，在炎性白细胞浸润附近瞬间爆发。目前尚不清楚趋化因子是否启动白细胞进入中枢神经系统组织，或放大鞘内炎症反应。为了解决这个问题，wt在CNS免疫介导炎症的最早证据中测定了趋化因子mrna的表达。在这些实验中，小鼠在免疫后的不同时间成对死亡。在牺牲时，每对中只有一人有EAE症状。症状的出现与牺牲时的组织学炎症密切相关。从大脑和脊髓两个中枢神经系统部位制备RNA，并通过灵敏定量的逆转录酶/聚合酶链反应斑点杂交法分析趋化因子mrna的表达。CNS MCP-1和IP-10基因表达与组织学炎症密切相关；事实上，在没有白细胞浸润的情况下，趋化因子的表达从未被检测到。原位杂交显示星形胶质细胞表达趋化因子转录物。这些发现为EAE免疫介导炎症过程中趋化因子mRNA表达的调控机制提供了新的信息，并与趋化因子作为中枢神经系统炎症反应放大器的作用一致。(C) 1995年学术出版社，inc .。
Central nervous system (CNS) expression of two chemokine mRNAs, encoding monocyte chemoattractant protein-1 (MCP-1) and IFN-gamma-inducible protein (IP-10), was previously shown to be closely related to the onset of clinical signs ofmurine experimental autoimmune encephalomyelitis (EAE). Chemokine mRNAs accumulated in a striking, transient burst within astrocytes, near inflammatory leukocyte infiltrates. It remained unclear if chemokines functioned to initiate leukocyte entry into CNS tissues, or to amplify the intrathecal inflammatory reaction. To address this issue, wt determined the expression of chemokine mRNAs at the earliest evidence of CNS immune-mediated inflammation. For these experiments, mice were sacrificed in pairs al varying times after immunization. Only one member of each pair was symptomatic for EAE at the time of sacrifice. Symptom presence correlated well with histological inflammation at the time of sacrifice. RNA was prepared from two CNS sites, brain and spinal cord, and expression of chemokine mRNAs was analyzed by a sensitive and quantitative reverse transcriptase/polymerase chain reaction dot-blot hybridization assay. CNS expressions of MCP-1 and IP-10 gene were correlated tightly with histological inflammation; indeed, chemokine expression was never detected in the absence of leukocyte infiltrates. In situ hybridizations showed that astrocytes expressed chemokine transcripts. These findings provide new information about mechanisms controlling chemokine mRNA expression during immune-mediated inflammation in EAE and are consistent with a role for chemokines as amplifiers of CNS inflammatory reactions. (C) 1995 Academic Press, lnc.